| Aim:Objective To observe the rat permanent focal cerebral ischemic injury after brain ischemia hemisphere cortex within the mammalian target of rapamycin(mammalian target of rapamycin,m TOR)expression of influence on the expression of LC3 and beclin-1 and explore the different routes of administration on the protective effect of ischemic brain injury in rats difference.Methods:Several healthy adult male Balb/c rats were selected and divided into two groups:control group,MCAO control group,intraperitoneal injection drug intervention group and intracranial injection drug intervention group.MCAO control group and intervention group with thread embolism method making permanent middle cerebral artery occlusion(permanent middle cerebral artery occlusion(MCAO)model,intraperitoneal drug intervention group rats in ischemia after making model(completed after MCAO)immediately after intraperitoneal injection of AMPK inhibitor compound C,MCAO control group and sham operation control group at the same time give the injection dose of solvent(saline + DMSO)intracranial intervention group rats were also at the same time off for intracranial injection of drugs.Rats in each group were taken at 24 h time point to the ipsilateral cortex.The expression of m TOR,LC3 and Beclin-1 were detected by blot Western method.To evaluate the effect of inhibiting AMPK activity on the ischemic brain injury in rats with behavioral symptoms and cerebral infarction volume.Results:Neural symptoms score showed that rats in the sham group showed no neurological symptoms,behavioral score 0;MCAO rats appear obvious neurological symptoms,behavioral score high,compared with the sham operation control group,with statistical significance(P < 0.01);intraperitoneal and intracerebral injection group and MCAO compared to the control group,the score was significantly lower(P< 0.01),suggesting that inhibition of AMPK activity can effectively reduce the MCAO rats of cerebral infarction after behavioral dysfunction.Intraperitoneal administration and intracranial injection compared with the control group,the score of abdominal group was lower than that of intracranial injection group(P<0.01).TTC staining results showed that: compared with the sham operation group,MCAO rats,cerebral infarction volume was significantly increased(P<0.01).Regardless of the abdominal to treatment group or intracranial administration group,MCAO rats compared to greatly reduce the volume of cerebral infarction(P < 0.01).It is suggested that the action of inhibiting AMPK activity can play a role in reducing the volume of cerebral infarction in MCAO rats.The degree of decline in the amount of intracranial when compared to the expression of the similarity between the compared to the results of Western blot results showed that beclin-1 protein expression level of MCAO group compared with the sham operation group was significantly increased(P<0.01)and abdominal group and group of intracranial expression in MCAO group showed decreased(P < 0.01),the two groups comparison with each other can be found in the latter protein expression decreased more(P < 0.01);LC protein expression trend and beclin-1 MCAO group compared to the sham operation group was significantly increased(P <0.01),but in the laparoscopic group and intracranial group can be found in MCAO group was decreased(P < 0.01).The two groups comparison with each other can be found in the experimental group was more(P<0.01).Expression of m TOR protein in MCAO group was the lowest(P 小于 0.01),and the expression level of the two groups was higher(P <0.01)than that in the groups.Conclusion:1.Permanent focal cerebral ischemia injury of rat induced autophagy activation and damage;2.The inhibition of AMPK activity to a certain degree of inhibition of autophagy.This mechanism makes inhibition of its activity plays a neuroprotective effect,inhibit neuronal autophagic death;3.Intracranial administration by intraperitoneal administration can be more obvious autophagy regulation to protect the effect of brain neurons. |
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